Neuronal reactivation of herpes simplex virus may involve interleukin-6.
Interleukin-6 (IL-6) is an inflammatory cytokine produced in many tissues, including the cornea and trigeminal ganglion. IL-6 acts by binding to its specific receptor, stimulating a cascade of signal proteins that induce the transcription factors NF-IL6 and STAT3. These IL-6-induced transcription factors change cellular gene transcription. Neutralization of IL-6 in vivo inhibits herpes simplex virus type 1 (HSV-1) ocular reactivation in mice. There are IL-6 response elements, possible binding sites of the IL-6 induced transcription factors, within the HSV-1 genome. These IL-6 response elements are concentrated in the inverted repeat regions of the genome, occurring in a non-random fashion in the promoters of the LAT and ICPO genes. Viral constructs containing deletions of IL-6 response elements in the LAT promoter region reactivate at a lower frequency compared with similar constructs lacking such deletions. HSV-1 may have evolved to exploit the relationship between a major inflammatory cytokine, IL-6, and conditions favorable for neuronal reactivation and subsequent replication in the epithelium. Exploring the role of IL-6, its receptor, and induced transcription factors in HSV-1 reactivation is a promising new avenue of research into the mechanism of HSV reactivation.
Kriesel
J D
JD
Department of Medicine, University of Utah School of Medicine, Salt Lake City 84132, USA.
Ricigliano
J
J
Spruance
S L
SL
Garza
H H
HH
Hill
J M
JM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000502:physiology; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D017874:Immediate-Early Proteins / Q000235:genetics; D015850:Interleukin-6 / Q000276:immunology / Q000502:physiology*; D051379:Mice; D009414:Nerve Growth Factors / Q000502:physiology; D009474:Neurons / Q000821:virology*; D011401:Promoter Regions, Genetic; D012367:RNA, Viral / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D050796:STAT3 Transcription Factor; D017384:Sequence Deletion; D015398:Signal Transduction; D018139:Simplexvirus / Q000235:genetics / Q000254:growth & development*; D015534:Trans-Activators / Q000502:physiology; D014158:Transcription, Genetic; D012668:Trigeminal Ganglion / Q000821:virology; D044767:Ubiquitin-Protein Ligases; D014775:Virus Activation / Q000502:physiology*; D017735:Virus Latency; D000093242:Interleukin-6 Inhibitors
D000911:Antibodies, Monoclonal; D004268:DNA-Binding Proteins; D017874:Immediate-Early Proteins; D015850:Interleukin-6; D009414:Nerve Growth Factors; D012367:RNA, Viral; D050796:STAT3 Transcription Factor; D015534:Trans-Activators; D044767:Ubiquitin-Protein Ligases; D000093242:Interleukin-6 Inhibitors; C494087:Stat3 protein, mouse; C051804:Vmw110 protein, Human herpesvirus 1